American journal of respiratory and critical care medicine最新文献

{"title":"Pulmonary Fibrosis-Related Genes in U.S. Veterans of African and European Ancestries.","authors":"Jessica A Peterson, Stephen Simeone, Susan K Mathai, Faye Pais, Susheela Hadigal, Qing Lu, Daniel Dochtermann, Diana Gomez-Manjarres","doi":"10.1093/ajrccm/aamag139","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag139","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A precision approach to translational research in acute lung injury.","authors":"Guillermo M Albaiceta, Claudia C Dos Santos, Rachel Zemans, Wolfgang M Kuebler","doi":"10.1093/ajrccm/aamag143","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag143","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early neutrophil and persistent eosinophil-associated gene signature in childhood asthma.","authors":"Francesco Foppiano, Andreas Böck, Claudia Beerweiler, Kathrin Urner, Markus Ege, Elisabeth Schmausser-Hechfellner, Chrysanthi Skevaki, Urs Frey, Josef Riedler, Remo Frei, Roger Lauener, Caroline Roduit, Anne M Karvonen, Marjut Roponen, Juha Pekkanen, Amandine Divaret-Chauveau, Cindy Barnig, Erika Von Mutius, Bianca Schaub","doi":"10.1093/ajrccm/aamag142","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag142","url":null,"abstract":"<p><strong>Rationale: </strong>Early childhood represents a critical window for asthma susceptibility, marked by developmental and molecular changes, yet their longitudinal pattern remains unclear.</p><p><strong>Objectives: </strong>To identify differences in longitudinal whole-blood gene expression during early childhood in future asthmatics compared to healthy children.</p><p><strong>Methods: </strong>We conducted a longitudinal whole-blood transcriptomic analysis at four timepoints (1, 4.5, 6, 10.5 years) in a sample of the birth cohort PASTURE (n = 378), comparing children who developed asthma between 6 and 10.5 years with non-asthmatic controls (83/295). Analyses included longitudinal differential gene expression, weighted gene co-expression network analysis, and cis-eQTL analysis.</p><p><strong>Measurements and main results: </strong>At age 1, 42 genes, mostly upregulated in future asthmatics, were associated with neutrophilic inflammation and NLRP3 inflammasome-markers. By 4.5 years, this shifted to a novel eosinophil-related signature (40 genes), remaining increased in asthmatics until 10.5 years. Co-expression analysis confirmed a neutrophilic module at 1 year and eosinophilic modules at 4.5, 6 and 10.5 years, all associated with asthma. Fractional exhaled nitric oxide was associated with the eosinophilic module at age 6 (P = .003). 86 SNPs were identified modulating the expression of 10 eosinophil-associated genes and GSDMB from this eosinophilic signature. A variant-based genetic risk score was associated with asthma diagnosis (aOR[95% CI]= 1.47[1.13-1.93]).</p><p><strong>Conclusion: </strong>We identified a shift from a neutrophil-driven gene signature at age 1 to a persistent eosinophilic signature at 4.5 to 10.5 years in asthmatic children, highlighting the 1 to 4.5-year period as most vulnerable period. Genetic variants strongly influenced the persistent eosinophilic gene signature, comprising potential novel therapeutic targets.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sotatercept and Prostacyclin De-Escalation in Stable Pulmonary Arterial Hypertension: A Single-Centre Case Series.","authors":"Victor M Moles, Thomas Cascino, Vallerie V McLaughlin","doi":"10.1093/ajrccm/aamag147","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag147","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxic niche drives lineage imbalance and early tumorigenesis in EGFR-mutant lung cancer.","authors":"Fanchen Meng, Zhijun Xia, Siwei Wang, Qian Wang, Meng Zhu, Jing You, Qinglin Wang, Ziyang Shen, Qinhong Sun, Jianyu Li, Zhitong Li, Pengcheng Zhu, Yuxiang Sun, Jie Wang, Qianghu Wang, Hongxia Ma, Tongyan Liu, Lin Xu, Rong Yin","doi":"10.1093/ajrccm/aamag150","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag150","url":null,"abstract":"<p><strong>Rationale: </strong>During tumorigenesis, approximately 20% of EGFR-mutant LUADs progress rapidly to aggressive subtypes. Multi-omics analyses of stage-I LUAD cohorts have revealed that centrally located lesions exhibit enhanced tumorigenic potential compared with peripheral counterparts, whereas the underlying mechanisms remain elusive.</p><p><strong>Objectives: </strong>To define the spatial-clinical determinants of early aggressive progression in EGFR-mutant LUAD and to develop a lineage-based mechanistic framework connecting regional microenvironmental constraints with epithelial cell-state remodeling and invasive acquisition.</p><p><strong>Methods: </strong>We conducted an integrated multi-omics analysis combining clinical cohort data (n = 277), single-cell and spatial transcriptomics, and functional studies in genetically engineered mouse models to identify spatial-clinical patterns. Mechanistic studies were carried out using mouse models, 3-D organoids, and controlled oxygen interventions to investigate the effects of hypoxia on cellular transformation.</p><p><strong>Measurements and main results: </strong>Our analysis revealed that centrally located lesions display enhanced tumorigenic potential compared to peripheral counterparts, driven by hypoxic niche. Hypoxic preconditioning (10% O2) induced ribosome collisions in EGFR-driven mouse models and organoids, activating the ZAKα-MAPK-c-Fos axis to disrupt alveolar lineage imbalance, characterizing as suppressing alveolar epithelial factor NKX2-1 while elevating stem-like progenitor FOXD1. Therapeutic hyperoxia (60% O2) restored lineage balance and attenuated tumorigenesis.</p><p><strong>Conclusions: </strong>A pre-existing hypoxic niche is a key spatial determinant of early malignant progression in EGFR-mutant LUAD, engaging ribosome-collision signaling through the ZAKα-MAPK-c-Fos axis and promoting alveolar lineage disruption. Restoring oxygenation, either through controlled hyperoxia or pharmacologic inhibition of this pathway, may help curb tumorigenesis and rapid progression of centrally located lesions.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravascular Large B-Cell Lymphoma Masquerading as Cryptococcosis.","authors":"Xinyue Huang, Ming Yang","doi":"10.1093/ajrccm/aamag151","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag151","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Guo et al., Dong et al., and Belecanech et al.","authors":"Laurent Savale, Thomas D'humières, Pablo Bartolucci, Marc Humbert","doi":"10.1093/ajrccm/aamag131","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag131","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidized Vitamin E Metabolites During Infancy and Childhood Asthma Risk: Too Little, Too Much, or Just Right?","authors":"Kedir N Turi, Tebeb Gebretsadik, Christian Rosas-Salazar, Tina V Hartert","doi":"10.1093/ajrccm/aamag144","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag144","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Many uncertainties Remain in the Longterm Care of SCD-PH.","authors":"Ryan Belecanech, Sophie Lanzkron, Elizabeth S Klings","doi":"10.1093/ajrccm/aamag133","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag133","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mast Cells and Endothelial Cells Mediate Interleukin-33 and ST2 Responses in Distal COPD Lungs.","authors":"Cecilia K Andersson, Premkumar Siddhuraj, Jimmie Jönsson, Johan Ahlgren, Caroline Lindö, Josquin A Nys, Ian C Scott, Sandra Lindstedt, Roland Kolbeck, Alison A Humbles, René Lutter, Y S Sabogal Piñeros, René E Jonkers, Ellen Tufvesson, Caroline Sandén, E Suzanne Cohen, Jonas S Erjefält","doi":"10.1093/ajrccm/aamag079","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag079","url":null,"abstract":"<p><strong>Rationale: </strong>Information is missing on the tissue cell expression patterns of interleukin IL-33 (IL-33) and splice variants of the IL-33 receptor ST2 in normal and COPD lungs.</p><p><strong>Objectives: </strong>To characterize the expression patterns of IL-33, the soluble ST2 (sST2) and membrane-bound ST2 (ST2L) splice variants in the poorly studied small airway and distal lung compartments in COPD and controls.</p><p><strong>Methods: </strong>Surgically excised lung tissue was collected from 38 COPD patients and 21 non-COPD controls. Lung compartment expression of IL-33 and ST2 and key expressing cell types were assessed histologically by combined in situ hybridization and multiplex immunohistochemistry. Expression dynamics of IL-33, ST2L and sST2 were explored by spatially resolved single-cell analysis.</p><p><strong>Measurements and main results: </strong>COPD lungs displayed increased IL-33 mRNA and IL-33 mRNA/protein ratios, suggesting increased IL-33 turnover. Total ST2/IL1RL1 mRNA levels were upregulated in COPD lungs. Mast cells constituted the major ST2-expressing immune cell population in controls and displayed a microenvironmental-specific upregulation of both ST2L and sST2 in COPD. In control alveolar regions, ST2Lhigh sST2high mast cells were present alongside IL-33-expressing general capillary (gCAp) and sST2moderate ST2Llow aerocyte (aCap) endothelial subsets. In COPD patchy alveolar regions displayed markedly elevated capillary sST2 and numbers of ST2L + and IL-33 + gCaps.</p><p><strong>Conclusions: </strong>By unravelling the expression patterns of IL-33 and the biologically opposing ST2L and sST2 splice variants in control and COPD lungs, the present study provides novel insights into IL-33-mediated immunity in the distal lung, information that has bearing on treatments strategies targeting this pathway in lung diseases.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":19.4,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}